The Role of Nrf2: Oxidative Stress and Cancer
Oxidative stress because of imbalance between ROS detoxification and production plays a critical role in determining cell fate. In reaction to this excess ROS, apoptotic signaling pathway is triggered to promote normal cell death. But through deregulation of biomolecules, higher quantity of ROS promotes carcinogenesis in cells with faulty signaling variables. Within this line, NRF2 is apparently as a master regulator, which protects cells from oxidative and electrophilic stress. Nrf2 is a intracellular transcription factor that modulates the expression of a range of genes to synthesize anti-oxidative enzymes, fatty factors, anti-apoptotic proteins and drug transporters. Under normal condition, Nrf2 is often degraded in cytoplasm by interaction with Keap1 inhibitor as an adaptor for ubiquitination variables. But, higher quantity of ROS triggers tyrosine kinases to dissociate Nrf2: Keap1 complex, nuclear export of Nrf2 and coordinated stimulation of cytoprotective gene expression. But deregulation of Nrf2 and/or Keap1 because of mutation and triggered upstream oncogenes is associated with nuclear accumulation and constitutive activation of Nrf2 to protect cells from apoptosis and cause proliferation, metastasis and chemoresistance. Owning into the interplay of both ROS and Nrf2 signaling pathways together with carcinogenesis, Nrf2 modulation appears to be significant at the personalization of cancer treatment.Keywords: Antioxidant; Cancer; Keap1; Nrf2; Oxidative stress; ROS.